Skip to main content
. 2020 Nov 10;25(22):5227. doi: 10.3390/molecules25225227

Table 1.

Overview of the here discussed multivalent aptamers developed for different diseases. The specific linker between different aptamer motifs is highlighted in bold. For dimeric and multimeric constructs, the enhancement in binding affinity or activity is also reported. In LD201* aptamer, the underlined sequence is the one conserved from the original LD201 aptamer and the nucleobases in italics are those removed in the design of mΔ1. In the sequence of TD05.17 aptamer, locked nucleic acid (LNA) residues are highlighted in red. In OSJ-T3-LNA-OMe sequence, LNA and 2′-OMe RNA nucleobases are marked in red and blue, respectively. In VEa5 and Vap7 aptamers, the sequence derived from the primer regions are shown in italic lower case letters.

Anti-inflammatory aptamers
Name Sequence (5′ →3 ′) Features Ref.
LD201 CAAGGTAACCAGTACAAGGTGCTAAACGTAATGGCTTCG Kd: 1.8 nM [59]
LD174 CATTCACCATGGCCCCTTCCTACGTATGTTCTGCGGGTG Kd: 5.5 nM
LD196 TGGCGGTACGGGCCGTGCACCCACTTACCTGGGAAGTGA Kd: 3.1 nM
LD201* GCGGTAACCAGTACAAGGTGCTAAACGTAATGGCGC IC50: 8 nM Tm: 48.7 °C [61]
mΔ1 GCCAGTACAAGGTGCTAAACGTAATGGC IC50: 10.6 nM Tm: 55.7 °C
dΔ1-A3 mΔ1-AAA-mΔ1 IC50: 12 nM;
No enhancement vs. mΔ1
dΔ1-A9 mΔ1-AAAAAAAAA-mΔ1 IC50: 0.3 nM;
ca. 35-fold enhancement vs. mΔ1
dΔ1-A15 mΔ1-AAAAAAAAAAAAAAA-mΔ1 IC50: 1.6 nM;
ca. 7-fold enhancement vs. mΔ1
dΔ1-A20 mΔ1-AAAAAAAAAAAAAAAAAAAA-mΔ1 IC50: 1.6 nM;
ca. 7-fold enhancement vs. mΔ1
tΔ1-A9 mΔ1-AAAAAAAAA-mΔ1-AAAAAAAAA-mΔ1 IC50: 0.8 nM;
ca. 13-fold enhancement vs. mΔ1
Antiviral aptamers
Name Sequence (5′ →3 ′) Features Ref.
1 OH-(CGGAGG)4-TEL EC50: > 5 [78]
2 O-DMT-(CGGAGG)4-TEL EC50: 0.54
3 O-pGlc-(CGGAGG)4-TEL EC50: > 5
Anticoagulant aptamers
Name Sequence (5′ →3 ′) Features Ref.
TBA15 GGTTGGTGTGGTTGG Tm: 33 °C PT: 25.7 s; [109]
AA 5′-TBA-A-3′-3′-A-TBA-5′ Tm: 37 °C PT: 32.6 s;
ca. 1.3-fold enhancement vs. TBA
TT 5′-TBA-T-3′-3′-T-TBA-5′ Tm: 33 °C PT: 29.6 s;
ca. 1.2-fold enhancement vs. TBA
gly 5′-TBA-3′-gly-3′-TBA-5′ Tm: 35 °C No enhancement vs. TBA
AglyA 5′-TBA-A-3′-gly-3′-A-TBA-5′ Tm: 35 °C PT: 30.5 s;
ca. 1.2-fold enhancement vs. TBA
TglyT 5′-TBA-T-3′-gly-3′-T-TBA-5′ Tm: 29 °C No activity
TBA GGTTGGTGTGGTTGG Kd: 7.10 nM [111]
TBA29 AGTCCGTGTAGGGCAGGTTGGGGTGACT Kd: 2.40 nM
HD1-22 TBA15-A15-TBA29 Kd: 0.65 nM;
ca. 11-fold enhancement vs. TBA15 and 4-fold vs. TBA29
Linker 0 TBA15-TBA29 Kd: 0.14 nM;
ca. 144-fold enhancement vs. TBA15 and 25-fold vs. TBA29 		[112]
Linker 5 TBA-T5-TBA29 Kd: 0.06 nM;
ca. 337-fold enhancement vs. TBA15 and 58-fold vs. TBA29
Linker 10 TBA-T10-TBA29 Kd: 0.74 nM;
ca. 27-fold enhancement vs. TBA15 and 5-fold vs. TBA29
Linker 20 TBA-T20-TBA29 Kd: 0.35 nM;
ca. 58-fold enhancement vs. TBA15 and 10-fold vs. TBA29
A1(12nm)A2 TBA29-(spacer 18)5-TBA15 Kd: 0.3 nM;
ca. 13-fold enhancement vs. TBA15 and 10-fold vs. TBA29 		[113]
A1(24nm)A2 TBA29-(spacer 18)10-TBA15 Kd: 0.06 nM;
ca. 67-fold enhancement vs. TBA15 and 48-fold vs. TBA29
A2(24nm)A1 TBA15-(spacer 18)10-TBA29 Kd: 0.03 nM;
ca. 133-fold enhancement vs. TBA15 and 97-fold vs. TBA29
RNV216A TBA15/iT TCT: 27 s; [114]
RNV219 TBA29/ iT TCT: 19 s;
RNV220 RNV216A-TEG-RNV219 TCT: 40 s;
ca. 1.5-fold enhancement vs. RNV216A and 2-fold vs. RNV219
RNV220-T RNV216A-TTTT-RNV219 TCT:30 s;
ca. 1.1-fold enhancement vs. RNV216A and 1.6-fold vs. RNV219
TBV-08 AGCAGCACAGAGGTCAGATG-TBA15-TGAGACCTTGCATGCGACTTGGTGAGCACGTGAGA-TBA29-CCTATGCGTGCTACCGTGAA Kd: 8.1 pM;
ca. 308-fold enhancement vs. TBA15 and 185-fold vs. TBA29 		[115]
16T TBA15-T16-TBA29 Kd: 120 pM;
ca. 21-fold enhancement vs. TBA15 and 13-fold vs. TBA29
Bi-4S TBA27-(S)4-TBA15 2903 cps/sec;
No enhancement 		[116]
Bi-6S TBA27-(S)6-TBA15 97 cps/sec;
ca. 11-fold enhancement vs. TBA15
Bi-8S TBA27-(S)8-TBA15 63 cps/sec;
ca. 17-fold enhancement vs. TBA15
Bi-10S TBA27-(S)10-TBA15 346 cps/sec;
ca. 3-fold enhancement vs. TBA15
Anticancer aptamers
Name Sequence (5′→3 ′) Features Ref.
VBA-01 AATAAACGCTCAACTCAAGTGGCGTGCGGCAGGTTGGTGTGACGGCTGGGAGGGTTCGACATG Kd: 405 nM [177]
DVBA-01 VBA-01-duplexDNA-VBA-01 Kd: 485 nM: no enhancement
DVBA/Dox DVBA-01 + Dox Kd: 28 nM;
ca. 14-fold enhancement vs. VBA-01
TD05 ACCGTGGAGGATAGTTCGGTGGCTGTTCAGGGTCTCCTCCACGGT Kd: 359 nM at 4 °C [185]
TD05.1 AGGAGGATAGTTCGGTGGCTGTTCAGGGTCTCCTCCT Kd: 53 nM at 4 °C;
Kd > 10,000 nM at 37 °C
TD05.17 AGGAGGATAGTTCGGTGGCTGTTCAGGGTCTCCTCCT Kd: 43 nM at 4 °C:
Kd > 10,000 nM at 37 °C
TVA.8S TD05.1-(sp18)8-TD05.1-(sp18)8-TD05.1 Kd: 490 nM at 37 °C;
ca. 20-fold enhancement vs. TD05.1
TetVA.8S TD05.1-(sp18)8-TD05.1-(sp18)8-TD05.1-(sp18)8-TD05.1 Kd: 425 nM at 37 °C;
ca. 24-fold enhancement vs. TD05.1
L-BVA.8S sp18-TD05.17-(sp18)8-TD05.17-sp18 Kd: 6222 nM at 37 °C;
ca. 1.6-fold enhancement vs. TD05.17
L-TVA.8S sp18-TD05.17-(sp18)8-TD05.17-(sp18)8-TD05.17-sp18 Kd: 256 nM at 37 °C;
ca. 40-fold enhancement vs. TD05.17
L-TetVA.8S sp18-TD05.17-(sp18)8-TD05.17-(sp18)8-TD05.17-(sp18)8-TD05.17-sp18 Kd: 272 nM at 37 °C;
ca. 36-fold enhancement vs. TD05.17
R1.2 CACTGGGTGGGGTTAGCGGGCGATTTAGGGATCTTGAGTGGT Kd: 35.5 nM at 4 °C;
Kd: 65.6 nM at 37 °C		 [189]
R1.3 CACTGGGTGGGGTTAGCGGGCGATTTAGGGATCTT Kd: 134 nM at 4 °C
DR1.2_3S R1.2-(spacer)3-R1.2 Kd: 55.8 nM at 4 °C: no enhancement
Kd: 11.4 nM at 37 °C;
ca. 6-fold enhancement vs. R1.2 		[191]
DR1.2_5S R1.2-(spacer)5-R1.2 Kd: 31.7 nM at 4 °C; ca. 1.1-fold enhancement vs. R1.2
Kd: 20.8 nM at 37 °C; ca. 3.1-fold enhancement vs. R1.2
DR1.2_7S R1.2-(spacer)7-R1.2 Kd: 23.9 nM at 4 °C; ca. 1.5-fold enhancement vs. R1.2
Kd: 48.6 nM at 37 °C; ca. 1.3-fold enhancement vs. R1.2
ZUCH-1 ATCGTCTGCTCCGTCCAATACCGCGGGGTGGGTCTAGTGTGGATGTTTAGGGGGCGGTTTGGTGTGAGGTCGCGCG Kd: 3 nM [194]
OSJ-T1 CCAATACCGCGGGGTGGGTCTAGTGTGGATGTTTAGGGGGCGGTTTGG Kd: 2.3 nM [195]
OSJ-T2 CCAATACCGCGGGGTGGGTCTAGTGTGGATGTTTAGGGGGCGGTATTGG Kd: 2.7 nM
OSJ-T3 GCCGCGGGGTGGGTCTAGTGTGGATGTTTAGGGGGCGGC Kd: 2.1 nM
OSJ-T3-LNA-OMe AGCCGCGGGGTGGGTCTAGTGTGGATGTTTAGGGGGCGGCU Kd: 1.7 nM
OSJ-dimer-2S OSJ-T3-LNA-OMe-(S)2-OSJ-T3-LNA-OMe Kd: 0.5 nM; ca. 3.4-fold enhancement vs. OSJ-T3-LNA-OMe
OSJ-dimer-4S OSJ-T3-LNA-OMe-(S)4-OSJ-T3-LNA-OMe Kd: 0.3 nM; ca. 5.7-fold enhancement vs. OSJ-T3-LNA-OMe
OSJ-dimer-6S OSJ-T3-LNA-OMe-(S)6-OSJ-T3-LNA-OMe Kd: 0.4 nM; ca. 4.3-fold enhancement vs. OSJ-T3-LNA-OMe
OSJ-dimer-8S OSJ-T3-LNA-OMe-(S)8-OSJ-T3-LNA-OMe Kd: 1.7 nM: no enhancement
VEa5 ATACCAGTCTATTCAATTGGGCCCGTCCGTATGGTGGGTGTGCTGGCAGATAGTATGTGCAATCA Kd: 130 nM [210,211]
del5-1 ATACCAGTCTATTCAATTGGGCCCGTCCGTATGGTGGGTGTGCTGGCCAG Kd: 476 nM [112]
SL2-B CAATTGGGCCCGTCCGTATGGTGGGT Kd: 37.9 nM [213]
VEa5 homodimer VEa5-VEa5 Kd: 6.2 nM;
ca. 21-fold enhancement vs. VEa5 		[112]
del5-1 homodimer del5-1-del5-1 Kd: 17.2 nM;
ca. 28-fold enhancement vs. del5-1 		[112]
SL2-B homodimer SL2-B-SL2-B Kd: 14 nM;
ca. 2.7-fold enhancement vs. SL2-B 		[213]
2G19 CTGGCCAGGTACCAAAAGATGATCTTGGGCCCGTCCGAATGGTGGGTGTTCTGGCCAG Kd: 52 nM [214]
2G19 homodimer 2G19-2G19 Kd: 2.0 nM;
ca. 26-fold enhancement vs. 2G19
bivalent SL5 SL5-SL5 1.9 nM;
ca. 27-fold enhancement vs. 2G19
trivalent SL5 SL5-SL5-SL5 0.37 nM;
ca. 141-fold enhancement vs. 2G19
H4 TTACGTCAAGGTGTCACTCCCTAGGGGTCCAGGCGAAGCTTAGTAGGGGTGTCCCCTCCCAGAAGCATCTCTTTGGCGTG Kd: 4 nM [215]
H4 homodimer H4-T100-H4 Kd: 1.4 nM;
ca. 2.9-fold enhancement vs. H4
+5′G+3′C GCCCGTCTTCCAGACAAGAGTGCAGGG C Kd: 9.9 nM [213]
+5′G+3′C homodimer +5′G+3′C-T20-+5′G+3′C Kd: 5.5 nM;
ca. 1.8-fold enhancement vs. +5′G+3′C
+5′G+3′C homodimer +5′G+3′C-T60-+5′G+3′C Kd: 7.0 nM;
ca. 1.4-fold enhancement vs. +5′G+3′C
Vap7 ATACCAGTCTATTCAATTGCACTCTGTGGGGGTGGACGGGCCGGGTAGATAGTATGTGCAATC Kd: 20 nM vs. VEGF165;
Kd: 1.0 nM vs. VEGF121 		[218]
V7t1 TGTGGGGGTGGACGGGCCGGGTAGA Kd: 1.4 nM vs. VEGF165;
Kd: 1.1 nM vs. VEGF121
3R02 TGTGGGGGTGGACTGGGTGGGTACC Kd: 0.3 nM vs. VEGF165 [221]
3R02 homodimer 3R02-T10-3R02 Kd: 0.03 nM vs. VEGF165;
ca. 10-fold enhancement vs. 3R02
del5-1/V7t1 heterodimer del5-1-V7t1 Kd: 0.47 nM;
ca. 1000-fold enhancement vs. del5-1 and 3-fold vs. V7t1 		[218]
CLN0003_SL1 (SL1) ATCAGGCTGGATGGTAGCTCGGTCGGGGTGGGTGGGTTGGCAAGTCTGAT Kd: 123 nM [232]
ss-0 ATCAGGCTGGATGGTAGCTCGGTCGGGGTGGGTGGGTTGGCAAGTCTGAT−CGTGTCACGGATGGTAGCTCGGTCGGGGTGGGTGGGTTGGCAGTGACACG n.d. [233]

Kd: Dissociation constant; Tm: Melting temperature; DMT: 4,4′-dimethoxytrityl; pGlc: Glucosyl-4-phosphate group; TEL: tetra-end-linked; PT: Prothrombin time; gly: Glycerol residue; TCT: Thrombin clotting time; TEG: tetraethylene glycol; Cps: Scattering intensity; n.d.: Not determined.